Dexmedetomidine and Dexamethasone as Adjuvants to the Local Anesthetic Mixture in Rhomboid Intercostal and Sub-Serratus Block for Video-Assisted Thoracoscopic Surgery: A Randomized, Double-Blind, Controlled Trial.

Background: The utilization of adjuvants such as dexamethasone and dexmedetomidine in combination with local anesthetics has proven effective in extending analgesia duration. We aimed to investigate the potential efficacy of combining dexmedetomidine and dexamethasone in rhomboid intercostal and sub-serratus (RISS) block for prolonging postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS). Methods: We did this randomized, double-blind, controlled trial in two tertiary-care hospitals. A total of eighty-eight patients undergoing VATS under general anesthesia were enrolled in this study. They were randomly assigned into four groups: ropivacaine (R) group, ropivacaine + dexmedetomidine (RM) group, ropivacaine + dexamethasone (RS) group, or ropivacaine + dexmedetomidine + dexamethasone (RSM) group. The primary outcome measure was the duration of analgesia. Secondary outcomes included Numeric Rating Scale (NRS) scores, cumulative oxycodone consumption, and adverse effects. Results: The RSM group exhibited a significantly prolonged duration of analgesia at 1073.5 min (932.0-1283.3) compared to the R group with a duration of 154.5 min (80.5-199.3) and the RS group with a duration of 282.0 min (195.3-350.0, P < 0 0.001). The cumulative oxycodone consumption during the 0-12 hours and 0-24-hours period was significantly reduced in the RSM group compared to the R group (P < 0.05). There was also a lower incidence of nausea at 48 hours postoperatively in the RSM group compared to the RM group. However, there were no significant differences between the four groups regarding NRS pain scores. Conclusion: The combination of ropivacaine, dexmedetomidine, and dexamethasone in RISS block significantly prolongs the duration of postoperative analgesia following VATS.

Application of Multi-Channel Synchronized Dynamic Strain Gauges in Monitoring the Neutral Axis Position and Prestress Loss of Box Girder Bridges.

The aim of this paper was to explore the application of multi-channel synchronized dynamic strain gauges in monitoring the neutral axis (N.A.) position of prestressed concrete box girders. The N.A. position has recently been proposed as an indicator for monitoring the health of bridge structures. Laboratory experiments were conducted on a prestressed T-beam under different prestress level conditions to investigate the correlation between the prestress magnitude and the N.A. position. In the development of the multi-channel synchronized dynamic strain gauges, edge computing was employed to significantly reduce the amount of data transmitted from the sensor nodes on-site. In edge computing, only the dynamic strain response caused by the maximum vehicle load in each minute is transmitted. This approach greatly enhances the monitoring efficiency and enables the realization of on-site non-computer-based monitoring systems. The laboratory test results of the prestressed T-beam showed that the N.A. position tends to move slightly downward as the prestress force increases. In other words, when the prestress force decreases due to loss, the N.A. position exhibits a slight upward movement. This study selected a newly constructed prestressed box girder as the subject for on-site measurement of the N.A. position using multi-channel synchronized dynamic strain gauges shortly after the prestress was applied. The on-site monitoring data indeed revealed a gradual upward movement of the N.A. position. This phenomenon confirmed that soon after the completion of prestressed concrete bridges, there is a gradual loss of prestress due to the significant shrinkage and creep effects of the early-age concrete. The on-site monitoring result aligned with the findings from the laboratory experiments, where the N.A. position was observed to move upward as the prestress decreased.

Targeting inhibition of TCTP could inhibit proliferation and induce apoptosis in AML cells.

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein, which participates in many important physiological processes. Recently, the roles of TCTP in cell proliferation and apoptosis, especially its close relationship with various tumors, have attracted widespread attention. In this study, we found that the protein level of TCTP was significantly reduced in acute promyelocytic leukemia cell line NB4 transfected with retinoic acid-induced gene G (RIG-G). The RIG-G was found in our previous work as a key mediator of anti-proliferative activity in retinoid/interferon-related pathways. Here, we tried to further explore the function of TCTP in the development of acute myeloid leukemia (AML) from different levels. Our results showed that inhibiting TCTP expression could attenuate AML cells proliferation and induce apoptosis both in AML cell lines and in xenograft of NOD-SCID mice. In addition, either compared with patients in complete remission or non-leukemia patients, we detected that the expression of TCTP was generally high in the fresh bone marrow of AML patients, suggesting that there was a certain correlation between TCTP and AML disease progression. Taken together, our study revealed the role of TCTP in AML development, and provided a potential target for AML treatment.

Neuroinflammation-induced parvalbumin interneuron and oscillation deficits might contribute to neurobehavioral abnormities in a two-hit model of depression.

Depression is a common neuropsychiatric disorder that causes profound disability worldwide, yet the underlying mechanism remains unclear. Thus, the present study aimed to evaluate the effects of a two-hit model of depression on glial activation, parvalbumin (PV) interneuron, oscillation activity, and behavior alternations, and whether chronic fluoxetine treatment can reverse these abnormalities. Male mice were submitted to lipopolysaccharide (LPS) injection, followed by a modified chronic unpredictable stress (CUS) protocol. In our study, we showed that mice exposed to LPS and CUS exhibited reduced body weight, anhedonic-like behavior as well as cognitive and anxiety symptoms. These behavioral alternations were related to enhanced neuroinflammation, as reflected by significantly increased IL-1ß and IL-6 levels and microglia activation in the prefrontal cortex (PFC). In addition, mice exposed to LPS and CUS displayed significantly decreased PV expression and disturbance of theta and gamma oscillations in the PFC. However, chronic fluoxetine treatment reversed most of these abnormalities. In conclusion, our study suggests that neuroinflammation-induced PV interneuron and oscillation deficits might contribute to neurobehavioral abnormalities in a two-hit model of depression.

Integrated Proteomic and Phosphoproteomic Analysis of the Hippocampus in a Mouse Model of Early Life Inflammation.

INTRODUCTION: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment. METHODS: Both female and male mice received a single intraperitoneal injection of 100 µg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining. RESULTS: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis. CONCLUSIONS: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.

Application of Edge Computing in Structural Health Monitoring of Simply Supported PCI Girder Bridges.

This study proposes an innovative method for structural health monitoring of simply supported PCI girder bridges based on dynamic strain and edge computing. Field static and dynamic load tests were conducted on a bridge consisting of a span with newly replaced PCI girders and numerous spans with old PCI girders. Both the static and dynamic test results showed that the flexural rigidity of the old PCI girders decreased significantly due to deterioration. To improve the efficiency of on-site monitoring data transmission and data analysis, this study developed a smart dynamic strain gauge node with the function of edge computing. Continuous data with a sampling frequency of 100 Hz were computed at the sensor node. Among the computed results, only the maximum dynamic strain data caused by the passage of the heaviest vehicle within 1 min were transmitted. The on-site monitoring results indicated that under routine traffic conditions, the dynamic strain response of the new PCI girder was smaller than that of the deteriorated PCI girder. When the monitored dynamic strain response has a tendency to magnify, attention should be paid to the potential prestress loss or other deterioration behaviors of the bridge.

Higher serum PGE2 is a predicative biomarker for postoperative delirium following elective orthopedic surgery in elderly patients.

BACKGROUND: Postoperative delirium (POD), one of the most common complications following major surgery, imposes a heavy burden on patients and society. The objective of this exploratory study was to conduct a secondary analysis to identify whether there exist novel and reliable serum biomarkers for the prediction of POD. METHODS: A total of 131 adult patients (≥ 65 years) undergoing lower extremity orthopedic surgery with were enrolled in this study. Cognitive function was assessed preoperatively with Mini-Mental State Examination (MMSE). Delirium was diagnosed according to the Confusion Assessment Method (CAM) criteria on preoperative day and postoperative days 1-3. The preoperative serum levels of a panel of 16 biochemical parameters were measured by ELISA. RESULTS: Thirty-five patients developed POD, with an incidence of 26.7%. Patients in POD group were older (P = 0.001) and had lower preoperative MMSE scores (P = 0.001). Preoperative serum levels of prostaglandin E2 (PGE2, P < 0.001), S100ß (P < 0.001), glial fibrillary acidic protein (P < 0.001) and neurofilament light (P = 0.002) in POD group were significantly increased. Logistic regression analysis showed that advanced age (OR = 1.144, 95%CI: 1.008 ~ 1.298, P = 0.037), higher serum neurofilament light (OR = 1.003, 95%CI: 1.000 ~ 1.005, P = 0.036) and PGE2 (OR = 1.031, 95%CI: 1.018 ~ 1.044, P < 0.001) levels were associated with the development of POD. In addition, serum level of PGE2 yielded an area under the ROC curve (AUC) of 0.897 to predict POD (P < 0.001), with a sensitivity of 80% and a specificity of 83.3%. CONCLUSIONS: Our study showed that higher preoperative serum PGE2 level might be a biomarker to predict the occurrence of POD in elderly patients undergoing elective orthopedic surgery. TRIAL REGISTRATION: NCT03792373 www. CLINICALTRIALS: gov .

Identification of potential biomarkers for digestive system cancers from serum-derived extracellular vesicle RNA.

BACKGROUND: Poor prognosis of digestive system cancers is mainly owing to lack of accurate and timely diagnosis. The exploration of novel tumor biomarkers from extracellular vesicle (EV) might be helpful to clinical diagnosis for digestive system cancers. METHODS: Several public databases were first used for a preliminary screening of candidate genes. The RNA levels of these candidate genes were then detected in cancer cell lines and the patients serum-derived EVs by PCR Array or digital PCR, respectively. RESULTS: We found that 4 EV-RNAs, ANLN, ITGA6, KRT18, and MMP9, had a lower level in gastrointestinal cancer patients than in benign gastrointestinal diseases patients and healthy controls, while 3 EV-RNAs, ANLN, ITGA6, and KRT18, had a lower level in pancreatic cancer patients than in benign pancreatic diseases patients or healthy individuals. And EV-RNA of MMP9 had a relatively higher level in advanced pancreatic cancer patients than in early-stage patients. Moreover, ROC analysis demonstrated that the determination of the above EV-RNAs could increase the ability of traditional tumor biomarkers to distinguish benign and malignant diseases. CONCLUSIONS: The serum-derived EV-RNAs of ANLN, ITGA6, KRT18, and MMP9 could be served as novel, non-invasive biomarkers for digestive system cancers.

Parvalbumin interneuron-mediated neural disruption in an animal model of postintensive care syndrome: prevention by fluoxetine.

Postintensive care syndrome (PICS) is defined as a new or worsening impairment in cognition, mental health, and physical function after critical illness and persisting beyond hospitalization, which is associated with reduced quality of life and increased mortality. Recently, we have developed a clinically relevant animal model of PICS based on two-hit hypothesis. However, the underlying mechanism remains unclear. Accumulating evidence has demonstrated that hippocampal GABAergic interneuron dysfunction is implicated in various mood disorders induced by stress. Thus, this study investigated the role of hippocampal GABAergic interneurons and relevant neural activities in an animal model of PICS. In addition, we tested whether fluoxetine treatment early following combined stress can prevent these anatomical and behavioral pathologies. In the present study, we confirmed our previous study that this PICS model displayed reproducible anxiety- and depression like behavior and cognitive impairments, which resembles clinical features of human PICS. This behavioral state is accompanied by hippocampal neuroinflammation, reduced parvalbumin (PV) expression, and decreased theta and gamma power. Importantly, chronic fluoxetine treatment reversed most of these abnormities. In summary, our study provides additional evidence that PV interneuron-mediated hippocampal network activity disruption might play a key role in the pathology of PICS, while fluoxetine offers protection via modulation of the hippocampal PV interneuron and relevant network activities.

A Protocol for Cancer-Related Mutation Detection on Exosomal DNA in Clinical Application.

BACKGROUND: Recently, some genomic mutations in exosomal DNA have been found to be related to disease progress and clinical outcomes of patients in several cancers. Unfortunately, the methods for exosome isolation and exosomal DNA analysis are still lack of relevant research to ensure their optimal performance and the comparability. Here we aim to establish a protocol for cancer-related mutation detection on exosomal DNA in clinical application. METHODS: Taking KRAS mutation in pancreatic cancer as an example, we tested whether the types of blood samples, the potential factors in the courses of exosome isolation and exosomal DNA preparation, as well as the detail in mutation detection by droplet digital PCR (ddPCR) could influence the exosomal DNA analysis. RESULTS: We found that the concentration of exosomal DNA from serum was higher than that from plasma, whereas the mutant allele fraction (MAF) of KRAS in serum-derived exosomal DNA was obviously lower. The membrane-based method for exosome isolation showed no evident difference in both exosomal DNA yield and KRAS MAF from the classical ultracentrifugation method. DNase I pretreatment on exosomes could remove the wild-type DNA outside of exosomes and increase the KRAS MAF. PBS might interfere with the effect of DNase I and should not be recommended as resuspension buffer for exosomes if the subsequent experiments would be done with exosomal DNA. Besides, the denaturation of exosomal DNA before droplet generation during ddPCR could effectively improve the total KRAS copy number and mutation-positive droplet number. CONCLUSION: This study provides some methodological evidences for the selection of the optimal experimental conditions in exosomal DNA analysis. We also suggest a protocol for mutation detection on exosomal DNA, which might be suitable for the clinical testing and could be helpful to the comparison of results from different laboratories.

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer.

Background: Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes. Methods: Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis. Results: We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52, PSMA1, PSMA5, PSMB6, PSMA7, PSMA4, PSMA3, PSMB1, PSMA6, and FGA) were filtered from DEPs, most of which are proteasome subunits. Moreover, the validation data confirmed that PSMA3 and PSMA6 were explicitly enriched in the serum derived exosomes from patients with mGC. Conclusion: The present study provided a comprehensive description of the serum exosome proteome of mGC patients, which could be an excellent resource for further studies of mGC.

Neural network disturbance in the medial prefrontal cortex might contribute to cognitive impairments induced by neuroinflammation.

Neuroinflammation plays a key role in the progression of many neurodegenerative diseases, yet the underlying mechanism remains largely unexplored. Using an animal model of neuroinflammation induced by repeated lipopolysaccharide (LPS) injections, we found selectively reduced expression of parvalbumin (PV) but not somatostatin (SST) in the medial prefrontal cortex (mPFC). The reduced PV expression resulted in decreased intensities of vesicular GABA transporter and PV buttons, suggesting disinhibition in the mPFC. These further induced abnormal mPFC neural activities and consequently contributed to cognitive impairments. In addition, gamma oscillations supported by PV interneuron function were positively associated with time spent with the novel object in the novel object recognition test. Notably, down-regulation of neuroinflammation by microglia inhibitor minocycline or boosting gamma oscillations by dopamine 4 receptor agonist RO-10-5824 improved cognitive performance. In conclusion, our study proposes neural network disturbance as a likely mechanistic linker between neuroinflammation and cognitive impairments in neurodegeneration and possibly other psychiatric disorders.

Phytohormone dynamics in developing endosperm influence rice grain shape and quality.

Hormones are important signaling molecules regulating developmental processes and responses to environmental stimuli in higher plants. Rice endosperm, the portion of the seed surrounding the embryo, is the main determinant of rice grain shape and yield; however, the dynamics and exact functions of phytohormones in developing endosperm remain elusive. Through a systemic study including transcriptome analysis, hormone measurement, and transgene-based endosperm-specific expression of phytohormone biosynthetic enzymes, we demonstrated that dynamic phytohormone levels play crucial roles in the developing rice endosperm, particularly in regard to grain shape and quality. We detected diverse, differential, and dramatically changing expression patterns of genes related to hormone biosynthesis and signaling during endosperm development, especially at early developmental stages. Liquid chromatography measurements confirmed the dynamic accumulation of hormones in developing endosperm. Further transgenic analysis performed on plants expressing hormone biosynthesis genes driven by an endosperm-specific promoter revealed differential effects of the hormones, especially auxin and brassinosteroids, in regulating grain shape and quality. Our studies help elucidate the distinct roles of hormones in developing endosperm and provide novel and useful tools for influencing crop seed shape and yield.

IPyA glucosylation mediates light and temperature signaling to regulate auxin-dependent hypocotyl elongation in Arabidopsis.

Auxin is a class of plant hormone that plays a crucial role in the life cycle of plants, particularly in the growth response of plants to ever-changing environments. Since the auxin responses are concentration-dependent and higher auxin concentrations might often be inhibitory, the optimal endogenous auxin level must be closely controlled. However, the underlying mechanism governing auxin homeostasis remains largely unknown. In this study, a UDP-glycosyltransferase (UGT76F1) was identified from Arabidopsis thaliana, which participates in the regulation of auxin homeostasis by glucosylation of indole-3-pyruvic acid (IPyA), a major precursor of the auxin indole-3-acetic acid (IAA) biosynthesis, in the formation of IPyA glucose conjugates (IPyA-Glc). In addition, UGT76F1 was found to mediate hypocotyl growth by modulating active auxin levels in a light- and temperature-dependent manner. Moreover, the transcription of UGT76F1 was demonstrated to be directly and negatively regulated by PIF4, which is a key integrator of both light and temperature signaling pathways. This study sheds a light on the trade-off between IAA biosynthesis and IPyA-Glc formation in controlling auxin levels and reveals a regulatory mechanism for plant growth adaptation to environmental changes through glucosylation of IPyA.

KRAS Mutant Allele Fraction in Circulating Cell-Free DNA Correlates With Clinical Stage in Pancreatic Cancer Patients.

Background: The research on circulating tumor DNA (ctDNA) in pancreatic cancer (PC) has emerged recently. Although the detection rate of the KRAS mutation in ctDNA was relatively consistent with that in tumor tissue, whether the KRAS mutant allele fraction (MAF) differed was still not reported. So far, the clinical application of ctDNA detection in PC remains inconclusive. Methods: Plasma samples were collected from 110 PC and 52 pancreatic benign (PB) disease patients. The detection of KRAS mutation in ctDNA was performed using droplet digital PCR and compared with that in matched tumor tissue. We assessed the utility of KRAS MAFs in ctDNA and tissue for pancreatic malignancy assessment. Results: We found that KRAS MAF in ctDNA of PC patients was higher than that of PB patients, and was obviously associated with tumor staging and distant metastasis. However, KRAS MAF in ctDNA was significantly different from that in matched tissue. KRAS MAF in tumor tissue had no significant correlation with the clinical status. In addition, a ROC curve analysis revealed that mutant KRAS ctDNA combined with CA19-9 could increase the sensitivity rate of early-stage PC prediction, compared with CA19-9 test alone. Conclusion: The MAF of KRAS in ctDNA was related to the clinical stage of PC (p = 0.001). Mutant KRAS ctDNA could improve the sensitivity in early diagnosis of PC as a complement to CA19-9. Our study suggested that KRAS mutation in ctDNA could be a valuable circulating biomarker for the malignancy assessment in PC.

[Detection of Exosomal PML-RARA Fusion Gene Expression Level by Droplet Digital PCR].

OBJECTIVE: To establish a method for detecting the exosomal PML-RARA fusion gene expression by droplet digital PCR (ddPCR). METHODS: By using Taqman probe-based ddPCR technique, the method that able to detect both long and short isoforms of PML-RARA fusion gene transcripts was established. RNA from PML-RARA negative cell line HL-60 as negative control was used to set the limit of blank (LOB), while the RNA from PML-RARA positive cell line NB4 and the recombinant plasmid pSG5-PML-RARA(S) were used to set the limit of detection (LOD) for long and short PML-RARA transcripts, respectively. Furtherly, the expression of exosomal PML-RARA fusion gene in NB4 cell culture supernatant and serum of patients with acute promyelocytic leukemia (APL) was analyzed by ddPCR technique. RESULTS: The LOB of ddPCR assay for long and short PML-RARA transcripts were 0.0725 and 0.083 copies per microliter of PCR reaction system, respectively, while the LOD of long and short PML-RARA transcripts were 0.19 and 0.21 copies per microliter of PCR reaction system, respectively. In addition, the expression of exosomal PML-RARA fusion gene derived from both NB4 cell culture supernatant and serum of APL patients was successfully detected. CONCLUSION: A ddPCR-based technique for detecting fusion gene transcripts has been established, which can be used to analyze absolute quantification in the minimal quantity of PML-RARA transcripts derived from exosomes. It suggests the possibility of this technique to non-invasively and dynamicly monitore the exosomal PML-RARA transcripts from APL patients' serum.

A novel specific cleavage of IκBα protein in acute myeloid leukemia cells involves protease PR3.

IκBα protein plays an important role in NFκB signaling pathway regulation. The dysfunction of IκBα is tightly related to various diseases, including cancers. However, the molecular mechanisms by which IκBα loses its normal functions are diverse and complex. Here, we reported a novel cleavage of IκBα protein occurred in AML cells. Compared with the full-length IκBα protein, the truncated IκBα fragment exhibited a dramatically weak binding ability to NFκB complex and showed a significant decreased inhibition on NFκB transactivation. Knockdown of PR3, a serine protease mainly expressed in myeloid cells, could inhibit such IκBα cleavage and enhance the sensitivities of AML cells to the differentiation inducers. In addition, we showed that the level of PR3 mRNA was relatively higher in newly diagnosed AML patients than in those patients with complete remission, suggesting that PR3 expression and its involvement in IκBα cleavage might be closely associated with AML. Our studies revealed for the first time a PR3-involved IκBα cleavage in AML cells, providing some new evidences for further understanding the mechanisms underlying the deregulation of NFκB pathway in AML. Finally, we also suggested a potential clinical application value of PR3 protein in the treatment and prognosis surveillance for leukemia.

[Effects of Quercetin on Chronic Myeloid Leukemia Cell Line Resistant to Imatinib and Its Mechanism].

OBJECTIVE: To explore the growth inhibitory effect of quercetin on imatinib-resistant chronic myeloid leukemia cell lines and to clarify its involved mechanisms. METHODS: The cell viability was detected by trypan blue Staining, percentage of apoptotic cells and cell cycle distribution were detected by flow cytometry, the protein expression was detected by Western blot. RESULTS: Both inhibitory effect of proliferation and apoptosis-inducing effect were similar between the imatinib-resistant and -sensitive cell lines treated with 25 µmol/L quercetin for 24 hours and with arrest of cell cycle at G2/M phase. Quercetin could not change the expression of BCR-ABL. The expression of γ-H2AX was markedly enhanced and the phosphorylation of JNK up-regulated by quercetin in both imatinib-resistant and imatinib-sensitive cell lines. CONCLUSION: The growth of imatinib-resistant cells can be inhibited by quercetin, and the apoptosis of cells can be induced by quercetin, which may be related to cell cycle arrest in G2/M. The DNA damage and up-regulation of p-JNK may be involved in these processes.

Sertraline exerts its antitumor functions through both apoptosis and autophagy pathways in acute myeloid leukemia cells.

It has been found that sertraline, a widely used antidepressant drug, possessed antitumor roles in a variety of cancers including liver cancer, colorectal cancer and lymphoma. In this study, we provided evidences that sertraline had potent antiproliferative activity not only in acute myeloid leukemia (AML) cell lines but also in the fresh leukemia cells from AML patients, and could induce cell death through both apoptosis and autophagy pathways. Moreover, we found that inhibiting autophagy pathway could partially attenuate sertraline-induced apoptosis and cell growth inhibition, indicating that sertraline-induced autophagy process could facilitate AML cell apoptosis to some degree. However, blocking apoptosis pathway seemed no obvious effects on sertraline-caused autophagy as well as cell growth inhibition. Our results suggested a potential application value of sertraline in the treatment of AML patients, furnishing some perspectives for novel therapeutic strategies in leukemia.